E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal Osteoporosis |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Second extension
(1) To assess change from baseline in total hip BMD after 10 years of treatment.
(2) To assess safety and tolerability of long-term treatment. |
|
E.2.2 | Secondary objectives of the trial |
Second extension
- To assess change from baseline (randomization into base period) in BMD of lumbar spine, femoral neck, and trochanter.
- To determine the incidence of morphometrically assessed vertebral fractures.
- To determine the incidence of all clinical (both non-vertebral and vertebral) fractures.
- To assess changes from baseline (start of open-laber treatment) in BMD of lumbar spine, total hip, femoral neck, and trochanter during 5 years of treatment with odanacatib 50 mg once- weekly.
- To determine the incidence of morphometrically assessed vertebral fractures during 5 years of treatment with odanacatib 50 mg once-weekly.
- To determine the incidence of all clinical (both non-vertebral and vertebral) fractures during 5 years of treatment with odanacatib 50 mg once-weekly. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Second extension
In order to be eligible for participation in this trial, the subject must:
NOTE: Subjects inappropriately randomized into the trial (i.e., those who do not meet entry criteria) may be discontinued from the study at the discretion of the Sponsor.
1. Have met all initial inclusion criteria and ha ve not met any of the exclusion or discontinuation criteria of either the base or 1st extension studies.
NOTE: There is no specific BMD T-score required for eligibility in this extension study. If a subject has met excessive bone loss criteria at her end of study visit for the
1st extension study, or the 2nd extension screening visit, she can continue into this 2nd extension.
2. Be an active participant and have successfully completed the 1st extension study on study medication. (An interruption of approximately 12 weeks from the end of the first extension study to the begining of 2nd extension study is permissible).
3. Be assessed by the investigator as having had appropirate compliance during the base and 1st extension studies.
4. Have at least one hip (e.g. contains no hardware from or thopedic procedures) AND
suitable spinal anatomy that is evaluable by DXA.
5. Understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agree to participate by providing informed consent.
6. Be able to read, understand and complete questionnaires and diaries. NOTE: If a subject who understands the purpose and use of the diary
cards and study questionnaires is unable to complete these without assistance (e.g. due to visual problems, difficulty writing due to arthritis,
inability to read, etc.), a family member or care-giver may assist or may complete the diary card on her behalf
7. Be in generally good health, based on medical history, physical examination, and laboratory evaluation.
|
|
E.4 | Principal exclusion criteria |
Second extension:
The subject must be excluded from participating in the trial if the subject:
1. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the bes t interest of the subject to participate.
2. Is receiving treatment as follows:
1) Current use of osteoporosis therapy including: bisphosphonates, PTH, strontium, systemic estrogen + progestin, raloxifene or other SERM, RANK ligand inhibitor, or sub-cutaneous calcitonin. (Note: use of intranasal calcitonin is permitted.)
2) Subject is planning to initiate or is currently using long-term therapy (6 weeks or longer) with any CYP3A4 inducers (see Appendix 12.5 for examples).
3. Is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained or the subject cannot read or comprehend the written material.
4. Has participated in an investigational drug study other than the base study or 1st
extension study within the past 30 days.
5. Is currently a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Base study
Morphometric fractures, hip fractures, and clinical non-vertebral fractures.
Extension
The primary focus of this study will be on morphometic vertebral fractures. Lateral thoracic and lumbar spine radiographs will be obtained for each patient at baseline of the core study, Month 6, Month 12, and yearly thereafter until the end of the 5-year doubleblind extension study. The primary endpoint will be the first morphometrically assessed vertebral fracture per patient determined from these radiographs, analyzed as intervalcensored
survival data. All available x-ray data will be included in the analyses and time windows will be defined in a separate document to define timing, extending those of the core study.
Second extension:
For subjects with an allocation number ending in an odd number BMD will be measured at the hip and lumbar spine at screening, Month 72, Month 96, Month 120, Month 144 and end of study visits. For subjects with an allocation number ending in an even number BMD will be measured by DXA at the hip and lumbar spine at screening, Month 84, Month 108, Month 132 and end of study visits. DXA of the distal forearm and total body will still be performed for those subjects that had this measurement performed as part of their randomization visit in the base study when their BMD of the hip and lumbar spine are assessed. The primary endpoint of this extension study is the percent change from baseline in total hip BMD, in subjects originally randomized to a Odanacatib in the base study.
For the hip BMD measurement, the side of the hip measured must be consistent throughout the study. In case a change in hip side occurred in the base study, the change from the start of open-label treatment will be
calculated on the available hip side. If the hip side that is being measured becomes fractured during the study, then data of that hip side will be excluded from the time of the fracture onward.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 143 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |